Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs

Unbiased mapping of transcription factor binding sites along human chromosomes 21 and 22 points to widespread regulation of noncoding RNAs
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DOI:
10.1016/s0092-8674(04)00127-8
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发表时间:
2004-02-20
期刊:
影响因子:
64.5
通讯作者:
Gingeras, TR
Gingeras, TR
中科院分区:
生物学1区
文献类型:
--
作者:
Cawley, S;Bekiranov, S;Gingeras, TR

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使用高密度寡核苷酸阵列,代表人类染色体21和22上的所有非重复序列,我们以毫无偏见的方式将三种DNA结合转录因子(SP1,CMYC和p53)绘制为三个DNA结合转录因子,即SP1,CMYC和p53。该映射揭示了大量的转录因子结合位点(TFB)区域,SP1的估计值最小为12,000,而CMYC为25,000,而p53则为1600,当外推到整个基因组时。这些TFB的区域中只有22%位于蛋白质编码基因的5'末端,而36%位于特征良好的基因内或直接3'内,并且与非编码RNA显着相关。这些非编码RNA的大量响应是对视黄酸的调节,并且通常将重叠的蛋白质编码和非编码RNA对重叠。因此,人类基因组包含大致比较数量的蛋白质编码和非编码基因,这些基因受公共转录因子绑定并受公共环境信号调节。
Using high-density oligonucleotide arrays representing essentially all nonrepetitive sequences on human chromosomes 21 and 22, we map the binding sites in vivo for three DNA binding transcription factors, Sp1, cMyc, and p53, in an unbiased manner. This mapping reveals an unexpectedly large number of transcription factor binding site (TFBS) regions, with a minimal estimate of 12,000 for Sp1, 25,000 for cMyc, and 1600 for p53 when extrapolated to the full genome. Only 22% of these TFBS regions are located at the 5' termini of protein-coding genes while 36% lie within or immediately 3' to well-characterized genes and are significantly correlated with noncoding RNAs. A significant number of these noncoding RNAs are regulated in response to retinoic acid, and overlapping pairs of protein-coding and noncoding RNAs are often coregulated. Thus, the human genome contains roughly comparable numbers of protein-coding and noncoding genes that are bound by common transcription factors and regulated by common environmental signals.